New insights into the regulation of inflammation by adenosine
Joel Linden
Joel Linden
Published July 3, 2006
Citation Information: J Clin Invest. 2006;116(7):1835-1837. https://doi.org/10.1172/JCI29125.
View: Text | PDF
Commentary

New insights into the regulation of inflammation by adenosine

Abstract

Adenosine, long known as a regulator of cardiovascular function, has recently been identified as a significant paracrine inhibitor of inflammation that acts primarily by activation of A2A adenosine receptors (A2AARs) on lymphoid or myeloid cells. In this issue of the JCI, Yang et al. describe a proinflammatory phenotype resulting from deletion of the gene encoding the A2B adenosine receptor (A2BAR) in the mouse, suggesting that activation of the A2BAR can also have antiinflammatory effects (see the related article beginning on page 1913). Nevertheless, the role of the A2BAR remains enigmatic since its activation can either stimulate or inhibit the release of proinflammatory cytokines in different cells and tissues.

Authors

Joel Linden

×

Figure 1

Anti- and proinflammatory effects mediated by activation of the A2B AR.

Options: View larger image (or click on image) Download as PowerPoint
Anti- and proinflammatory effects mediated by activat...
(A) In macrophages, the release of TNF-α and other proinflammatory cytokines is inhibited as a result of activating either the A2AAR or the A2BAR. These effects are amplified if TNF-α production is stimulated by LPS, which signals through TLR4 and other Toll-like receptors. Activation of the A2BAR also stimulates production of the antiinflammatory cytokine IL-10. (B) In endothelial cells and other cells noted in Table 1, activation of the A2BAR stimulates IL-6 and other proinflammatory cytokines. Hypoxia increases the intracellular production of adenosine, which is transported outside the cell by nucleoside transport proteins. Hypoxia and possibly activation of the A2BAR stimulate the release of ATP and the production of the A2BAR and ectoenzymes (CD39 and CD73) that convert ATP to adenosine. Vasodilation in response to A2BAR activation may increase shear stress to stimulate ATP release.